Primary myoblasts from intrauterine growth-restricted fetal sheep exhibit intrinsic dysfunction of proliferation and differentiation that coincides with enrichment of inflammatory cytokine signaling pathways

Intrauterine growth restriction (IUGR) is linked to lifelong reductions in muscle mass due to intrinsic functional deficits in myoblasts, but the mechanisms underlying these deficits are not known. Our objective was to determine if the deficits were associated with changes in inflammatory and adrenergic regulation of IUGR myoblasts, as was previously observed in IUGR muscle. Primary myoblasts were isolated from IUGR fetal sheep produced by hyperthermia-induced placental insufficiency (PI-IUGR; n = 9) and their controls (n = 9) and from IUGR fetal sheep produced by maternofetal inflammation (MI-IUGR; n = 6) and their controls (n = 7). Proliferation rates were less (P \u3c 0.05) for PI-IUGR myoblasts than their controls and were not affected by incubation with IL-6, TNF-α, norepinephrine, or insulin. IκB kinase inhibition reduced (P \u3c 0.05) proliferation of control myoblasts modestly in basal media but substantially in TNF-α-added media and reduced (P \u3c 0.05) PI-IUGR myoblast proliferation substantially in basal and TNF-α-added media. Proliferation was greater (P \u3c 0.05) for MI-IUGR myoblasts than their controls and was not affected by incubation with TNF-α. Insulin increased (P \u3c 0.05) proliferation in both MI-IUGR and control myoblasts. After 72-h differentiation, fewer (P \u3c 0.05) PI-IUGR myoblasts were myogenin+ than controls in basal and IL-6 added media but not TNF-α-added media. Fewer (P \u3c 0.05) PI-IUGR myoblasts were desmin+ than controls in basal media only. Incubation with norepinephrine did not affect myogenin+ or desmin+ percentages, but insulin increased (P \u3c 0.05) both markers in control and PI-IUGR myoblasts. After 96-h differentiation, fewer (P \u3c 0.05) MI-IUGR myoblasts were myogenin+ and desmin+ than controls regardless of media, although TNF-α reduced (P \u3c 0.05) desmin+ myoblasts for both groups. Differentiated PI-IUGR myoblasts had greater (P \u3c 0.05) TNFR1, ULK2, and TNF-α-stimulated TLR4 gene expression, and PI-IUGR semitendinosus muscle had greater (P \u3c 0.05) TNFR1 and IL6 gene expression, greater (P \u3c 0.05) c-Fos protein, and less (P \u3c 0.05) IκBα protein. Differentiated MI-IUGR myoblasts had greater (P \u3c 0.05) TNFR1 and IL6R gene expression, tended to have greater (P = 0.07) ULK2 gene expression, and had greater (P \u3c 0.05) β-catenin protein and TNF-α-stimulated phosphorylation of NFκB. We conclude that these enriched components of TNF-α/TNFR1/NFκB and other inflammatory pathways in IUGR myoblasts contribute to their dysfunction and help explain impaired muscle growth in the IUGR fetus. Lay Summary-- Myoblasts are stems cells whose functional capacity can limit muscle growth. However, stressful intrauterine conditions cause these cells to be intrinsically dysfunctional. This restricts muscle growth capacity, leading to intrauterine growth restriction (IUGR) of the fetus, low birth weight, and less muscle mass after birth. Consequently, meat yield is reduced in IUGR-born food animals and glucose homeostasis is impaired in IUGR-born humans, which contributes to metabolic dysfunction. Intrinsic dysfunction of IUGR myoblasts has been previously observed, but the fetal programming changes (i.e., permanent changes in the development of cellular mechanisms that explains different functional outcomes) have not been identified. This study shows that one mechanism is the enhancement of signaling pathways for TNF-α and other inflammatory cytokines. These cytokines have roles in stress responses and regulation of muscle growth. Programmed enhancement of these pathways means that IUGR myoblasts are more responsive to even normal amounts of circulating cytokines. Unfortunately, the primary response of myoblasts to cytokines is slower differentiation (i.e., cellular transformation necessary for muscle growth). Programmed enhancement of this response directly impedes myoblast-dependent muscle growth, and the deficit is lifelong. However, identifying this mechanism is a fundamental step for developing strategies to improve muscle growth in low birth weight offspring

Failure to Detect Critical Auditory Alerts in the Cockpit: Evidence for Inattentional Deafness

Objective: The aim of this study was to test whether inattentional deafness to critical alarms would be observed in a simulated cockpit. Background: The inability of pilots to detect unexpected changes in their auditory environment (e.g., alarms) is a major safety problem in aeronautics. In aviation, the lack of response to alarms is usually not attributed to attentional limitations, but rather to pilots choosing to ignore such warnings due to decision biases, hearing issues, or conscious risk taking. Method: Twenty-eight general aviation pilots performed two landings in a flight simulator. In one scenario an auditory alert was triggered alone, whereas in the other the auditory alert occurred while the pilots dealt with a critical windshear. Results: In the windshear scenario, 11 pilots (39.3%) did not report nor react appropriately to the alarm whereas all the pilots perceived the auditory warning in the no-windshear scenario. Also, of those pilots who were first exposed to the no-windshear scenario and detected the alarm, only three suffered from inattentional deafness in the subsequent windshear scenario. Conclusion: These findings establish inattentional deafness as a cognitive phenomenon that is critical for air safety. Pre-exposure to a critical event triggering an auditory alarm can enhance alarm detection when a similar event is encountered subsequently. Application: Case-based learning is a solution to mitigate auditory alarm misperception

Negative emotional stimuli reduce contextual cueing but not response times in inefficient search

In visual search, previous work has shown that negative stimuli narrow the focus of attention and speed reaction times (RTs). This paper investigates these two effects by first asking whether negative emotional stimuli narrow the focus of attention to reduce the learning of a display context in a contextual cueing task and, second, whether exposure to negative stimuli also reduces RTs in inefficient search tasks. In Experiment 1, participants viewed either negative or neutral images (faces or scenes) prior to a contextual cueing task. In a typical contextual cueing experiment, RTs are reduced if displays are repeated across the experiment compared with novel displays that are not repeated. The results showed that a smaller contextual cueing effect was obtained after participants viewed negative stimuli than when they viewed neutral stimuli. However, in contrast to previous work, overall search RTs were not faster after viewing negative stimuli (Experiments 2 to 4). The findings are discussed in terms of the impact of emotional content on visual processing and the ability to use scene context to help facilitate search

Measurement of Longitudinal Spin Transfer to Lambda Hyperons in Deep-Inelastic Lepton Scattering

Spin transfer in deep-inelastic Lambda electroproduction has been studied with the HERMES detector using the 27.6 GeV polarized positron beam in the HERA storage ring. For an average fractional energy transfer = 0.45, the longitudinal spin transfer from the virtual photon to the Lambda has been extracted. The spin transfer along the Lambda momentum direction is found to be 0.11 +/- 0.17 (stat) +/- 0.03 (sys); similar values are found for other possible choices for the longitudinal spin direction of the Lambda. This result is the most precise value obtained to date from deep-inelastic scattering with charged lepton beams, and is sensitive to polarized up quark fragmentation to hyperon states. The experimental result is found to be in general agreement with various models of the Lambda spin content, and is consistent with the assumption of helicity conservation in the fragmentation process.Comment: 8 pages, 3 figures; new version has an expanded discussion and small format change

Beam-Induced Nuclear Depolarisation in a Gaseous Polarised Hydrogen Target

Spin-polarised atomic hydrogen is used as a gaseous polarised proton target in high energy and nuclear physics experiments operating with internal beams in storage rings. When such beams are intense and bunched, this type of target can be depolarised by a resonant interaction with the transient magnetic field generated by the beam bunches. This effect has been studied with the HERA positron beam in the HERMES experiment at DESY. Resonances have been observed and a simple analytic model has been used to explain their shape and position. Operating conditions for the experiment have been found where there is no significant target depolarisation due to this effect.Comment: REVTEX, 6 pages, 5 figure

Measurement of Angular Distributions and R= sigma_L/sigma_T in Diffractive Electroproduction of rho^0 Mesons

Production and decay angular distributions were extracted from measurements of exclusive electroproduction of the rho^0(770) meson over a range in the virtual photon negative four-momentum squared 0.5< Q^2 <4 GeV^2 and the photon-nucleon invariant mass range 3.8< W <6.5 GeV. The experiment was performed with the HERMES spectrometer, using a longitudinally polarized positron beam and a ^3He gas target internal to the HERA e^{+-} storage ring. The event sample combines rho^0 mesons produced incoherently off individual nucleons and coherently off the nucleus as a whole. The distributions in one production angle and two angles describing the rho^0 -> pi+ pi- decay yielded measurements of eight elements of the spin-density matrix, including one that had not been measured before. The results are consistent with the dominance of helicity-conserving amplitudes and natural parity exchange. The improved precision achieved at 47 GeV, reveals evidence for an energy dependence in the ratio R of the longitudinal to transverse cross sections at constant Q^2.Comment: 15 pages, 15 embedded figures, LaTeX for SVJour(epj) document class Revision: Fig. 15 corrected, recent data added to Figs. 10,12,14,15; minor changes to tex

The Flavor Asymmetry of the Light Quark Sea from Semi-inclusive Deep-inelastic Scattering

The flavor asymmetry of the light quark sea of the nucleon is determined in the kinematic range 0.02<x<0.3 and 1 GeV^2<Q^2<10 GeV^2, for the first time from semi-inclusive deep-inelastic scattering. The quantity (dbar(x)-ubar(x))/(u(x)-d(x)) is derived from a relationship between the yields of positive and negative pions from unpolarized hydrogen and deuterium targets. The flavor asymmetry dbar-ubar is found to be non-zero and x dependent, showing an excess of dbar over ubar quarks in the proton.Comment: 7 Pages, 2 figures, RevTeX format; slight revision in text, small change in extraction of dbar-ubar and comparison with a high q2 parameterizatio

Measurement of the Spin Asymmetry in the Photoproduction of Pairs of High-pT Hadrons at HERMES

We present a measurement of the longitudinal spin asymmetry A_|| in photoproduction of pairs of hadrons with high transverse momentum p_T. Data were accumulated by the HERMES experiment using a 27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h+h- pairs with p_T^h_1 > 1.5 GeV/c and p_T^h_2 > 1.0 GeV/c, the measured asymmetry is A_|| = -0.28 +/- 0.12 (stat.) +/- 0.02 (syst.). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.Comment: 5 pages (latex), 4 figures (eps

Observation of a Single-Spin Azimuthal Asymmetry in Semi-Inclusive Pion Electro-Production

Single-spin asymmetries for semi-inclusive pion production in deep-inelastic scattering have been measured for the first time. A significant target-spin asymmetry of the distribution in the azimuthal angle phi of the pion relative to the lepton scattering plane was observed for pi+ electro-production on a longitudinally polarized hydrogen target. The corresponding analyzing power in the sin(phi) moment of the cross section is 0.022 +/- 0.005 +/- 0.003. This result can be interpreted as the effect of terms in the cross section involving chiral-odd spin distribution functions in combination with a time-reversal-odd fragmentation function that is sensitive to the transverse polarization of the fragmenting quark.Comment: 5 pages of RevTex, 3 ps figures, 2 table